Combining cyclophosphamide (Cy) and corticosteroids has dramatically improved the prognosis of Wegener's granulomatosis (WG). But this treatment carries the risks of severe infectious complications and drug toxicity. During a 10-month period, we observed 6 cases of Pneumocystis carinii pneumonia (PCP) in 23 patients with biopsy-proven WG and renal involvement. These 23 patients were enrolled in a multicenter controlled clinical trial designed to evaluate the efficacy and safety of either intermittent high-dose pulse Cy or daily oral low-dose Cy in combination with oral prednisone. Mean delay of onset of PCP was 2.5 months after the beginning of the immunosuppressive therapy. In all cases, the diagnosis of PCP was established by cytological examination of bronchoalveolar lavage fluid. None of the patients experienced severe leukopenia at the time of diagnosis, but the mean lymphocyte count decreased to 495/mm3 (range 100 to 830/mm3) and 2 patients had inverted CD4/CD8 T-cell ratios. Renal function was significantly impaired (creatininemia = 493.5 vs 195.4 micromol/l; p = 0.03) in the 6 patients presenting PCP vs those without. High-dose co-trimoxazole therapy was successful in 3 patients, but 3 others who required mechanical ventilation died. Treatment of WG with daily prednisone and either pulse or oral Cy may have contributed to higher rates of PCP in the past than previously thought and, therefore, patients currently receiving such a regimen may be at greater risk for PCP. For these patients, this opportunistic infection must remain highly suspect in order to reach a diagnosis earlier and rapidly initiate treatment. In addition, recommendations for prophylactic therapy are needed.